Q J Med 2005; 98:729736 doi:10.

1093/qjmed/hci113

Advance Access publication 31 August 2005

Original papers
Analysis of an adult Duchenne muscular dystrophy population
A.E. PARKER1, S.A. ROBB2, J. CHAMBERS3, A.C. DAVIDSON1, K. EVANS1, J. ODOWD1, A.J. WILLIAMS1 and R.S. HOWARD1,4
From the 1Lane-Fox Unit, 3Department of Non-Invasive Cardiology and 4Department of Neurology, St Thomas Hospital, and 2Department of Paediatrics, Newcomen Centre, Guys Hospital, Guys and St Thomas Trust, London, UK
Received 19 January 2005 and in revised form 26 July 2005

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Summary
Background: Advances in management have led to increasing numbers of patients with Duchenne muscular dystrophy (DMD) reaching adulthood. Older patients with DMD are necessarily severely disabled, and their management presents particular practical issues. Aim: To review the management of a late adolescent and adult DMD population, and to identify areas in which the present service provisions may be inadequate to their needs. Design: Retrospective review. Methods: We studied 25 patients with DMD referred to an adult neuromuscular clinic over a 7-year period. Clinical details were obtained retrospectively, from case notes or direct observations. Results: There were 24 males and one symptomatic female carrier. Nine patients died during the observation period. There was no significant correlation between age of wheelchair confinement and age of death. Sixteen patients received noninvasive positive pressure support. Twelve attended mainstream schools and 12, residential special schools. All the patients lived at home for some or all of the time, when their main carers were either one or both of the parents. The most striking difficulties were with the provision of practical aids, including appropriate hoists and belts, feeding and toileting aids, and the conversion of accommodation. Patients rarely wished to discuss the later stages of their disease, and death was often more precipitate than expected. Death usually occurred outside hospital and the final cause was often difficult to establish. Discussion: Adult patients with DMD develop progressive impairment, due to respiratory, orthopaedic and general medical factors. However, the particular areas of difficulty in this study often reflected inadequate and poorly directed social and medical support, illustrating the need for improvements in the structure, co-ordination and breadth of rehabilitation services for adult patients with DMD.

Address correspondence to Dr R.S. Howard, Department of Neurology, St Thomas Hospital, Guys and St.Thomas Trust, London SE1 7EH. email: robin.howard@gstt.sthames.nhs.uk ! The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

730

A.E. Parker et al. treatment of medical complications. The number of out-patient visits ranged from 6 to 27, and the number of admissions from 0 to 12. FVC measurements were undertaken on each attendance, with the patient seated. This retrospective review was initially undertaken as an audit of the management of DMD. The diagnosis of DMD was made by a senior paediatric neurology consultant and confirmed by clinical and developmental progression consistent with DMD. A mean of 8 years of clinical case notes were reviewed. Initial diagnosis was made on the basis of clinical phenotype, out-of-frame mutation in the dystrophin gene and/or complete absence of dystrophin immunostaining on muscle biopsy. Consecutive patients were studied. Clinical details were obtained, retrospectively, from case notes or from direct observations by two of us (AP, RSH). We reviewed the developmental history, diagnostic criteria, neurological presentation, symptomatic and functional progression, social and educational provision and disease course. The 25 patients represent a subgroup of patients with DMD who were referred from a paediatric service because they had reached the age of 16. Other patients were transferred to local services, and some patients were seen both locally and at the LFRU clinic. These referrals were made irrespective of the progression and nature of their disease, although most patients did require respiratory management within the LFRU. The LFRU provides a multidisciplinary base for assessment, with most patients being seen by consultants in respiratory medicine, orthopaedics, cardiology and rehabilitation, as well as physiotherapists with considerable expertise in the management of neurological disability. There was close liaison with the MDC-funded family care officer, who attended most clinics. A specialist nurse was allocated to take particular responsibility for the DMD patients. The Lane Fox Unit is also a supraregional respiratory care centre with access to training, 24-h ventilatory support, and an in-patient unit for admission if necessary.

Introduction
Duchenne muscular dystrophy (DMD) is the most common childhood onset muscular dystrophy, with an incidence estimated to be 1:3500 live births. The condition is inherited in an X-linked manner, but one third of cases are due to a spontaneous mutation. The natural history is well understood, presenting a relentless, progressive deterioration in limb and trunk strength, confining the patient to a wheelchair around the age of 12, and leading to death in the early 20s, usually due to respiratory or cardiac complications. The disease is characterized by muscular weakness, but the expression of dystrophin isoforms in heart and brain leads to disease manifestations in these organ systems as well.13 Disease progression is inevitable, leading to a state of severe physical dependence. However, most adults with DMD remain fully competent, and maintain a robust approach to managing their disability. With increasing advances in respiratory,4 cardiac and orthopaedic care for muscular dystrophy, survival with DMD may be increasing.5,6 Appropriate care for an adult patient with Duchenne muscular dystrophy demands attention to the orthopaedic, respiratory and cardiac systems, irrespective of symptomatology, because deterioration in any of these areas can advance rapidly over the course of months. However, there is relatively little information concerning the management of the adult DMD population in the community. In particular, there is no clear understanding of the difficulties in adapting to leaving school, seeking employment or obtaining support appropriate to the level of disability. We retrospectively reviewed 25 patients with DMD referred to an adult neuromuscular clinic, aiming to identify areas of difficulty in the management of DMD in hospital and community settings.

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Methods
Patients with DMD (n 25) were seen in the neuromuscular clinic at The Lane Fox Respiratory Unit (LFRU) between 1996 and 2003, most being referred from the paediatric neuromuscular clinic between the ages of 16 to 20. Some of the patients had been seen in the Lane Fox Unit before transfer of their care, for respiratory assessments or for the management of respiratory complications. All the patients were assessed by a consultant neurologist (RSH) during out-patient appointments and were seen every 36 months; many were subsequently admitted electively for assessment, or acutely for

Results
Twenty-four of the patients were male; one was a symptomatic female carrier. The results presented below include only data from the male patients; the details of the female patient are described separately. Nine patients died during the observation period. Mean age of death (SD) was 21.4 10.1 years (range 1926). The mean age of the 16 patients alive

Duchenne muscular dystrophy at the end of the study was 22.1 5.2 years (range 1531). There were two sets of brothers.
Patient Exon
1 2 3 4 5 6 7 8 9 10 11 0

731

5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80

Diagnosis
Mean age at diagnosis was 4.6 3.5 years (range 19). Three patients had a known family history of the disease at the time of diagnosis, and they were diagnosed earlier (mean age 2.0 years, range 13). CK was elevated in all the patients at the time of diagnosis, and was the basis of the diagnosis in the patients with a family history. Fourteen patients had muscle biopsies. These showed a characteristic appearance of scattered groups of regenerating and necrotic muscle fibres, increased endomysial connective tissue and muscle fibre loss with fat replacement. Dystrophin deficiency was confirmed after straining muscles with dystrophin antibody. Four patients were noted to have had EMG examinations, all which showed myopathic changes.

Figure 1. Exons involved in our Duchenne muscular dystrophy patients. Black bars, deleted exons. Dark grey bars, exons potentially affected by confirmed out of frame mutations, Circle, exons affected by base insertions. Light grey bars, exons affected by heterozygosity in female patient.

Genetics
Genetic information was available for 15 patients. There were two sets of brothers affected. Nine patients were found to have deletions of the dystrophin gene, five patients were negative and one had a base insertion in exon 21 which led to a reading-frame shift (Figure 1).

Pattern of original illness

Median age of first walking was 18 months (range 1124), Gowers manoeuvre was observed at a median age of 5 years (range 1.57), calf hypertrophy was evident at 5 years (range 37), a waddling gait at 6 years (range 39) and toe walking at 7 years (range 211). Patients lost the ability to walk unaided at median age of 10 years (range 513) and became totally wheelchair-dependent at a median age of 11 years (range 713). In our patient group, there was no significant correlation between age of wheelchair confinement and age of death.

Early disease progression/orthopaedic deterioration

All patients received physiotherapy aimed at appropriate stretching; they were also offered night anklefoot orthoses (AFOs) when they developed Achilles tendon tightness. Seven of the patient underwent Achilles tendon release and rehabilitation in ischial weight-bearing knee-ankle-foot orthoses (KAFO) to prolong ambulation (mean age 9 years, range 711). One of the

patients underwent repeat Achilles tendon release to improve foot posture at the age of 18. Seven patients experienced significant fractures (total 16); in five these were multiple, and one patient had a hip dislocation. Nine of the fractures involved the lower limb, and three were upper-limb fractures; details were not available for the remaining patients. Eight of the thirteen fractures occurred after the patient was confined to a wheelchair. One of two patients had a lower-limb fracture while ambulant, and lost independent ambulation as a result. Scoliosis developed in 20/24 patients, and spinal surgery was recommended in fifteen. All recommendations were made between 14 and 16 years of age. Nine of these patients underwent spinal surgery and six refused. The details of the procedure are known for six of the patients. Complications of the procedure were noted in three patients. One patient had a wound infection with persistent aseptic discharge, one experienced neuropathic bladder urinary symptoms that later resolved, and one patient developed severe hip pain following the procedure. There was inadequate data to demonstrate any improvement in FVC or survival after spinal surgery, although all the patients who underwent surgery described that their seating position became much more comfortable and easier to adjust.

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Respiratory deterioration
There was a progressive fall in FVC in all the patients. The rate of decline was variable, but in most patients, the reduction was relatively consistent over several years. A sudden decline was occasionally precipitated by intercurrent events such as worsening scoliosis or infective complications linked to the development of hypoventilation.

732

A.E. Parker et al. hypertrophy. ST elevations or T wave inversion were seen in three patients, of whom one had ST depression at night on ambulatory ECG. One patient was noted to have a conduction delay, specifically a right-sided abnormality (RSR in V1/V2). Other conduction abnormalities included bradycardia/tachycardia syndrome due to sino-atrial disease in one patient, and VE or SVE on ambulatory ECG in two. Echographic data were available for 21 patients. Findings were normal in 11. In the abnormal group, the most common finding was left ventricular wall motion abnormalities: seen in seven patients, this ranged from dyskinesis to complete akinesis, and three were predominantly in the posterior or inferior regions. Two patients had significant dilatation, and seven had a reduced ejection fraction, from 50% to 25%. Four patients were receiving angiotensin-converting enzyme (ACE) inhibitors.

In 20 patients, FVC fell below 1 l due to progressive respiratory muscle weakness. This led to nocturnal hypoventilation in nine patients, daytime hypoxia and diurnal type II respiratory failure in six, and respiratory arrest in two. Bulbar weakness and difficulty clearing secretions led to episodes of aspiration and bronchopneumonia. Twelve patients experienced recurrent hospitalizations for respiratory infections. Overnight oximetry studies were undertaken if the FVC fell below 1 l, or if there were symptoms suggestive of sleep disordered breathing, including daytime hypersomnolence, lethargy or morning headache. Results were available for 17 patients. Nine of the 17 patients had significant desaturations during the night ranging from 90% to 53%. The major patterns seen in the study were REMassociated desaturation, increased heart rate variability suggestive of upper-airway-associated disease, a combination of the first two, normal studies, and highly disordered sleep breathing. The criteria used for commencing non-invasive ventilation were variable and depended upon the presence and severity of symptoms (sleepiness and morning headache), the absolute level of forced vital capacity, the presence of nocturnal hypoventilation, arterial blood gases, scoliosis and the level of home support. Sixteen of the 24 patients received nocturnal positive pressure ventilation (NIV), beginning at ages ranging from 13 to 26 years, with 10 commencing between 14 and 16 years. Another patient (at 16) started NIV at the end of the study. Generally, when started, NIV was used for 810 h overnight but, in some patients, symptoms of increasing breathlessness occurred during the day, necessitating increased use of NIV, such that four patients required full-time ventilatory support. Six patients had ENT problems (i.e. rhinitis or ulceration of the nasal bridge) using the face mask. Four patients were intubated and ventilated during episodes of respiratory failure; of these, one died but three were successfully extubated, and no patient had a tracheostomy. Seven patients were receiving NIV at the time of their death.

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Occupational and educational

Eight patients were documented to have associated cognitive developmental disability, although detailed cognitive assessment was only available for two patients. Four were described as having global developmental delay, two had mild learning disabilities, and two had late speech development. One additional patient had ongoing speech difficulties that were attributed to a language barrier, as Bengali was his native tongue and the language spoken at home. Twelve attended mainstream schools with individual support workers and adaptations to deal with the special educational needs caused by their disability and any cognitive difficulties. The level of adaptation and the extent to which schools were able to cope with the demands of severe disability was highly variable. Eight patients left school or attended irregularly after the age of 12. Twelve attended residential special schools, including five of those with cognitive disabilities. In general, their integration was satisfactory, and these patients found their schooling successful. Six of the 24 boys achieved success in public examinations, with two attending university, and three others, Colleges of Higher Education. Only one patient was able to sustain employment in mainstream work, but two were actively seeking employment at the end of the study.

Cardiac deterioration
Seven of the 18 patients with available data had sinus tachycardia present on either ECG (4 patients) or 24-h ambulatory ECG (3 patients). Seven other patients had evidence of precordial abnormalities, which included tall R waves in anterior leads, right ventricular dominance, or right axis deviation; two of these met criteria for right ventricular

Other health concerns

There were a number of other symptomatic complaints among the patients in our study.

Duchenne muscular dystrophy The most common were gastrointestinal symptoms, experienced by at least twelve patients. Six patients experienced severe and intractable constipation, four patients had dysphagia, and two patients had gastro-oesophageal reflux. Six patients were markedly overweight (BMI 4 25), four were severely underweight and one required percutaneous endoscopic gastroscopy. Three of the patients who were severely underweight required NIV. Eight patients had urinary complaints, including frequency and incontinence. They experienced considerable difficulties in using a bottle. Co-existing disease included epilepsy (n 1), type II diabetes (n 1), and thyrotoxicosis (n 1). Two patients had hearing difficulties.

733

Preparation for death and cause of death

Patients and their families were aware of disease progression and usually understood the natural history of the condition. Nonetheless, and understandably, patients rarely wished to discuss the later stages of their disease. Death was often more precipitate than expected, and usually a consequence of some sudden overwhelming respiratory infection or other intercurrent event. In some, there was a clear progressive deterioration of ventilatory function, with the gradual progression of CO2 narcosis. Seven of the nine patients who died were receiving NIV at the time of their death. In these patients, NIV was commenced at a slightly older age (range 1721) and they had received support for 13 years at the time of death. However, there remains considerable uncertainty about the way in which these patients used NIV during the later stages of their illness. Death usually occurred outside hospital, and the final cause was often difficult to establish. There were no cases in whom sudden cardiac death was known to have occurred, but this cannot be excluded.

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Social support
All the patients lived at home for some or all of the time, at which time their main carers were either one or both of the parents; however, only four patients were documented as also having support from external carers. There were several reasons for inadequate external support: on occasions, local social services failed to provide adequate assessment or did not understand the complex needs of patients; in other circumstances, the patient or their carers refused extra support. The most striking difficulties were with the provision of practical aids, including appropriate hoists and belts, feeding and toileting aids and the conversion of accommodation. The carers of all the patients in this series expressed dissatisfaction concerning the delay or failure in provision of simple aids recommended by the appropriate therapist or from the clinic, with a delay in the provision of more complex needs, such as an appropriate bed, being in excess of two years. All the patients had electric wheelchairs, but the size of the chair and the seating arrangements were a frequent cause for concern, as was the delay experienced by many in obtaining modifications. Other difficulties included adaptation of foot rests, and table adjustment of hand controls. Three patients were provided with environmental control systems (ECS). Most patients received full provision of disability allowances, but full access to social services provision was inadequate, and often depended on the input of the muscular dystrophy key worker. All the patients had access to the local muscular dystrophy care worker, who provided considerable practical support in accessing available financial, domiciliary and clinical information.

Female carrier case

There was one symptomatic female carrier who presented to the clinic. She is now 42 years old. She was diagnosed at age 7 on the basis of clinical features, EMG and muscle biopsy. Diagnosis was confirmed by the presence of a deletion of exons 13 to 17 in one dystrophin allele. On gene dosage analysis, her phenotype was attributed to nonrandom X inactivation. She became wheelchairdependent at the age of 13 years, and at 31 she began nocturnal non-invasive positive pressure ventilation.

Discussion
This study describes a retrospective review of consecutive patients with DMD seen in an adult clinic over a seven-year period. The data on some patients were incomplete, as the patients were evaluated at multiple centres during the course of their illness, or had missing notes. In particular, it was difficult to obtain details of death in those who had died outside hospital. The Newcastle Muscle Centre7 looked at a series of 25 new diagnoses of DMD in the absence of a family history. In this group, the mean age at diagnosis was 4 years and 10 months, ranging from 16 to 99 months. Mean age of walking for the 24 boys who did walk was 17.7 months, ranging

734

A.E. Parker et al. had experienced fractures, of which half were among independently ambulatory patients.9 Scoliosis develops early in nearly all children with DMD,10 and is usually progressive, especially when the patient becomes wheelchair-bound and during the growth spurt. Early spinal stabilization is indicated, which is associated with significant complications.1113 Scoliosis was common in this series, and spinal surgery was discussed with most patients in the present series but was rejected by several, who did not wish to consider an extensive surgical procedure. Also, a number of patients were not considered for such intervention because respiratory or cardiac involvement was already advanced. While surgical correction of the curve clearly improves nursing care and quality of life by allowing more comfortable wheelchair posture,14,15 its effects on pulmonary function and life expectancy are controversial.16,17 Several studies have shown no change in the rate of decline of pulmonary function following curve correction,14,16 while Galasko, et al. (1992)17 described stabilization of pulmonary function for up to 36 months after spinal surgery, and improved survival. In the present series, there was no significant improvement in FVC following surgery, but patients all reported that seating was more comfortable.

from 21 to 24 months. In the present series, age of first walking and at diagnosis were not significantly different from those in the Newcastle and previous studies (18 months and 5 years, respectively). Although there is evidence of longer survival, particularly with the increased use of NIV and better scoliosis management, the overall progression of the condition has not changed. The demographic pattern and disease progression, in the present series, is compatible with other series. In the present series, the diagnostic criteria varied. A striking elevation in CK reflects the primary damage at the sarcolemmal membrane, with leak of CK out of muscle fibre, and is seen in all patients. EMG is not needed to identify a myopathic process when the CK is high, but may be important to excluding neurogenic cause. However, the definitive diagnosis of DMD is made by muscle biopsy and DNA analysis. In the present series, biopsy was undertaken in 14 patients and was diagnostic.

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

Orthopedic deterioration
In the present series there was considerable physiotherapy input, with at least 6-monthly review from presentation until transfer to the adult clinic. This aimed to maintain mobility and standing for as long as possible, as well as preventing the development of contractures. The transition from childhood to adolescence is characterized by a loss of mobility and an increasing dependence on assistive technology to maintain independence and minimize the need for assistance. Appropriate stretching of the Achilles tendon, iliotibial bands, knee and hip extensors and flexors was undertaken on a regular basis, where possible as a home programme, to delay onset of contractures. Night-time AFOs were used at the onset of Achilles tendon shortening, and daytime AFOs once the child was chair-dependent. Longitudinal studies show that loss of strength, specifically in hip extension and ankle dosiflexion, are the primary predictors of loss of ambulation.8 Rehabilitation in ischial weight-bearing KAFOs was considered in all boys at loss of ambulation, but not taken up on some because of personal/family preference, extensive contractures, or insufficient residual strength (notably in the hip abductors), the latter often due to delayed presentation following loss of ambulation. In the present series, fractures were very common and often led to precipitate deterioration in mobility, although only one patient were confined to a wheelchair after the fracture. This contrasts with another study looking at fracture prevalence, which found that 20.9% of the 378 patients in the study

Respiratory deterioration
Respiratory disease is an almost inevitable complication in the adult patient, and is the underlying cause of death in 70% of DMD patients. It is the primary result of restrictive disease stemming from inspiratory muscle weakness, severe scoliosis, reduced lung and chest wall compliance, an ineffective cough due to respiratory muscle weakness, and obstructive sleep apnoea.10,1820 Non-invasive nasal ventilation (NIV) increases survival in hypercapnic patients with DMD21,22 and ameliorates symptoms.23 Life expectancy is 51 year once diurnal hypercapnia develops, but with NIV it increases to 85% at 1 year, and 73% at 5 years.5,6 Furthermore patients who initially require invasive IPPV part time often go on to use it full time for a mean of 6.3 4.6 years.24 Importantly, most patients with DMD who receive chronic ventilatory assistance express satisfaction with their quality of life, despite the extent of their physical dependence.24 The relatively late occurrence of respiratory failure, often in association with bulbar weakness, makes it desirable to avoid IPPV via a tracheostomy, despite the advantages of providing airway access.25 In the present series, there was a characteristic and predictable deterioration in FVC

Duchenne muscular dystrophy with time, leading to nocturnal hypoventilation, daytime hypoxia and the development of type II respiratory failure. All the patients who developed nocturnal hypoventilation were successfully treated with nocturnal NIV, leading to a marked improvement in their ventilatory function and quality of life. The patients used NIV for increasing times during the daytime as their respiratory function deteriorated. In no patient was a tracheostomy undertaken. The use of NIV did not prevent the development of aspiration and bronchopneumonia, which was the usual cause of death.

735

Cardiac deterioration
Cardiac complications are common in DMD. Cardiomyopathy is due to the progressive replacement of myocardial fibres by connective tissue, which tends to occur predominantly in the posteriobasal and lateral regions of the left ventricle, sparing the right ventricle and atrium.2630 In the present series, typical electrocardiographic findings included tall right percordial R waves, an increased R/S ratio and deep Q waves in leads I, aVL, and V5-6, reflecting posterior left ventricular damage resulting from the characteristic DMD cardiomyopathic changes described above.31 Echocardiography showed left ventricular abnormalities, with hypokinesis or dyskinesis in seven and dilatation in two. The excessive weight of six DMD patients led to severe management difficulties with both appropriate chair provision and transferring. A further three patients had further weight loss either as a consequence of dysphagia or of poor appetite. Percutaneous endoscopic gastrostomy (PEG) was necessary in two. In DMD, full-scale verbal and performance IQs are normally distributed, with means approximately one standard deviation below the normal population mean and non-progressive.32 There may be selectively poor performance on tests requiring comprehension of complex verbal information, with other weakness in arithmetic and vocabulary subtests compared to other verbal, performance or memory measures.33 In the present series, eight patients were identified with significant cognitive impairment. Formal psychometric assessment is recommended if learning difficulties are suspected, in order to maximize educational achievement. Bushby, et al.34 observed that a higher than expected proportion of families with DMD were from socio-economically deprived backgrounds, even at the time of first diagnosis. In the present series, we did not systematically study socioeconomic demography but it is our impression that

many families were from a socially deprived background and our patients certainly experienced similar difficulties in accessing the sustained, highquality, specialised support necessary for the successful management of the condition. Parents and patients occasionally rejected offers of further support from carers. This was generally because they doubted that the carers would be adequately trained to cope with the needs of such complex and severe disability. There was often a reluctance from local health provision to support the funding of such carers. This emphasizes the importance of both providing adequate funding for carers but also of ensuring carers are appropriately trained in techniques of managing patients disabled by neuromuscular weakness. Death was often relatively unexpected, usually as a consequence of some sudden overwhelming respiratory infection or other intercurrent event. In some, there was clearer progressive deterioration of ventilatory function with the gradual progression of CO2 narcosis. The management of patients in the later stages of their disease and their parents is often extremely difficult and fraught. The level and nature of discussion must be tailored to the needs of the individual family. The process of informing patients and their families is long, and requires the support of a multidisciplinary team including nurses, therapists and care workers, but the responsibility for ensuring that the family is fully informed and all their questions are answered ultimately lies with the physician. The family must be prepared for the development of bronchopneumonia and ventilatory failure, and they must have clear guidance about if, when and where the patient is to be admitted to hospital. The admitting unit must be aware of the policy discussions concerning ventilatory and palliative management of the terminal stages. In the present series, this may be extremely difficult because patients often live a long way from the unit primarily responsible for the management. It is therefore essential that local services, including GP, carers and therapists are able to provide clear management guidance if the patient is admitted to a local A&E department as an emergency. Advances in orthopaedic, respiratory and cardiological care have led to a major change in the outlook for patients with DMD reaching adolescence. With appropriate support, they can continue to live fulfilling and rewarding lives despite profound neuromuscular weakness and consequent disability. The present study suggests that, in the UK, society is lagging behind in its ability to provide appropriate support to allow these patients to remain independent in the community and to afford their families the necessary back-up. Vigorous

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010

736

A.E. Parker et al.

spinal surgery on lung function in Duchenne muscular dystrophy. Thorax 1995; 50:11738. 17. Galasko CSB, Delaney C, Morris P. Spinal stabilization in Duchenne Muscular Dystrophy. J Bone Joint Surg 1992; 74B:21014. 18. Smith PEM, Calverley PMA, Edwards RHT, Evans GA, Campbell EJM. Practical problems in the respiratory care of patients with muscular dystrophy. N Engl J Med 1987; 316:1197205. 19. Khan Y, Heckmatt JZ. Obstructive apnoeas 1. Duchenne muscular dystrophy. Thorax 1994; 49:15761. 20. Hukins CA, Hillman DR. Daytime predictors of sleep hypoventilation in Duchenne Muscular dystrophy. Am J Respirat Crit Care Med 2000; 161:16670. 21. Raphael J-C, Chavret S, Chastang, et al. Randomised trial of preventive nasal ventilation in Duchennes muscular dystrophy. Lancet 1994; 343:16004. 22. Gomez-Merino E, Bach JR. Duchenne Muscular Dystrophy: Prolongation of life by noninvasive ventilation and mechanically assisted coughing. Am J Phys Med Rehabil 2002; 81:41115. 23. Howard RS, Wiles CM, Hirsch NP, Spencer GT. Respiratory involvement in primary muscle disorders: assessment and management. Q J Med 1993; 86:17589. 24. Bach JR, Ishikana Y, Kim H. Prevention of pulmonary morbidity for patients with Duchenne Muscular dystrophy. Chest 1997; 112:10248. 25. Howard RS, Davidson C. Long term ventilation in neurogenic respiratory failure. J Neurol Neurosurg Psychiat 2003; 74(suppl. 3):iii 2430. 26. Melacini P, Vianello A, Villanova C, Fanin M, Miorim M, Angelini C, Dalla Volta S. Cardiac and Respiratory involvement in advanced stage Duchenne muscular dystrophy. Neuromuscular Disorders 1996; 6:36776. 27. Muntoni F. Cardiac complications of childhood myopathies. J Child Neurol 2003c; 18:191202. 28. Muntoni F. Cardiomyopathy in muscular dystrophies. Current Opinions in Neurology 2003b; 16:57783. 29. Perloff JK, Henze E, Schelbert HR. Alterations in regional myocardial metabolism, perfusions, and wall motion in Duchenne muscular dystrophy studied by radionucleotide imaging. Circulation 1984; 69:3342. 30. Finsterer J, Stollberger C. The heart in human dystrophinopathies. Cardiology 2003; 99:119. 31. Corrado G, Lissoni A, Beretta S, et al. Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhtymias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol 2002; 89:83841. 32. Cotton S, Voudouris N, Douglas J. Key findings from a meta-analytical study on intellectual function in Duchenne muscular dystrophy. J Intellect Disab Res 2000; 44:248. 33. Hinton VJ, De Vivo DC. Poor verbal working memory across intellectual level in boys with Duchenne dystrophy. Neurology 2000; 54:212732. 34. Bushby K, Simon R, ODonnell S, Steele JG. Social deprivation in Duchenne Muscular dystrophy: a populationbased study. Br Med J 2001; 323:10356.

lobbying on behalf of these patients is already undertaken by special interest organisations such as The Muscular Dystrophy Association, but it is incumbent on all professionals involved in their care to ensure that their non-clinical needs are also appropriately met.

References
1. Emery A. The muscular dystrophies. Oxford, Oxford University Press, 2001. 2. Emery AE. The muscular dystrophies. Lancet 2002; 359:68795. 3. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2003; 12:73140. 4. American Thoracic Society. Respiratory care of the patient with Duchenne Muscular5 Dystrophy. Am J Respir Crit Care Med 2004; 170:45665. 5. Simmonds AK, Muntoni F, Heather S, Fielding S. Impact of nasal ventilation on survival in hypocapnic Duchenne muscular dystrophy. Thorax 1998; 53:94952. 6. Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromusc Disord 2002; 12:9269. 7. Bushby KMD, Hill A, Steele JG. Failure of early diagnosis in symptomatic Duchenne Muscular Dystropky. Lancet 1999; 353:5578. 8. Bakker JPJ, de Groot IJM, Beelen A, Lankhorst GJ. Predictive factors of cessation of ambulation in patients with Duchenne muscular dystrophy. Am J Phys Med Rehab 2002; 81: 90612. 9. MacDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Fracture Prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 2002; 44:6958. 10. Smith AD, Koreska J, Moseley CF. Progression of scoliosis in Duchenne Muscular Treatment. J Bone Joint Surg 1989; 71A:1197205. 11. Do T. Orthopaedic management of the muscular dystrophies. Curr Opin Paediatrics 2002; 14:503. 12. Marsh A, Edge G, Lehovsky J. Spinal fusion in patients with Duchennes muscular dystrophy and a low forced vital capacity. Eur Spine J 2003; 12:50712. 13. Ramirez N, Richards S, Warren P, et al. Complications after posterior Spinal Fusions in Duchenne Muscular Dystrophy. J Paediatric Orthopaedics 1997; 17:10913. 14. Miller RG, Chalmers AC, Dao H, Filler Katz A, Holman D, Bost F. The effect of spine fusion on respiratory function in Duchenne Muscular Dystrophy. Neurology 1991; 41:3840. 15. Shapiro F, Sethna N, Colan S, Wohl ME, Specht L. Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. Muscle Nerve 1992; 15:60414. 16. Declan Kennedy J, Staples AJ, Brook PD, Parsons DW, Sutherland AD, Martin AJ, Stern LM, Foster BK. The effects

Downloaded from qjmed.oxfordjournals.org by guest on October 23, 2010